Fever in a teenage traveller.
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Adolescent↗
Biomedical subjects
D Campbell
Publications and source records attributed to D Campbell.
The use of snowboard boot bindings in a hip disarticulation prosthesis.
This report describes a new technique for fastening a hip disarticulation socket. It was developed at the request of the patient who needed to fasten his prosthesis using only one hand, because of a left upper limb disability. Snowboard boot bindings were secured to the socket of the prosthesis and allowed it to be securely fastened and released using his dominant hand only. The design of the bindings permitted a high closing force with minimum one-handed effort by the user.
Adult↗
Health services research: what is it and what does it offer?
Over the last 20 years, clinical medicine has witnessed rapid expansion in its underlying evidence base, greater demand for accountability in clinicians' use of limited resources and increasing societal expectation for health care that confers proven benefit at reasonable cost to all eligible recipients. Health services research, also referred to as the clinical evaluative sciences, has grown in response to the need for objective empirical analysis of the modern health system's ability to deliver effective, efficient, equitable and safe care and to further the health and well-being of whole populations. In this article we provide an overview of the aims, methods and outputs of this burgeoning new discipline.
Australia↗
Functional retinotopy of monkey visual cortex.
The operations of primary visual cortex generate continuous representations of orientation, ocular dominance, and retinotopy that, to fit in two dimensions, organize at separate but overlapping scales (e.g., 20-500 microm, 200 microm to 5 mm, and 2-33 mm). Where their scales overlap, these organizations interact; iso-orientation contours cross ocular dominance columns at right angles, and ocular dominance columns distort retinotopy near the V1/V2 border. To explore these interactions, we developed an optical technique for visualizing retinotopy in vivo that allows us to analyze it in relation to ocular dominance and orientation patterns. Our results show local retinotopic distortions in every region of macaque V1 that we examine, including regions far from the V1/V2 border. They also show a consistent relation between local axes of distortion and ocular dominance slabs, which they intersect at angles of approximately 90 degrees. A further correlation is provided by retinotopic maps from New World primates that show less distortion (9 vs 60%) in two species characterized by an absence of pronounced ocular dominance columns. Retinotopic maps from these New World primates also revealed an unexpected tilt of the vertical midline representation that diverged from the V1/V2 border by an angle of approximately 20 degrees. Overall, these results suggest a general tendency for slab-based organizations to distort retinotopy by representing the same part of space more than once in adjacent slabs.
Animals↗
Epstein-Barr virus encoded latent membrane protein-1 induces epithelial cell proliferation and sensitizes transgenic mice to chemical carcinogenesis.
EBV is found to be associated with 100% of poorly or undifferentiated nasopharyngeal carcinomas, a tumor of epithelial origin. The latent membrane protein-1 (LMP1) of EBV, may play a causal role in the development of this disease. The experiments initiated here were designed to examine the activity of LMP1 in vivo in the epidermis of PyLMP1 transgenic mice in relation to its putative role in carcinogenesis. Transgenic positive epidermis showed a 2-3-fold increase in the mitotic index, coupled with an increased level of expression of proliferative cytokeratin markers (K6 and K14) over controls. These results provide direct evidence that LMP1 induces proliferation in otherwise normal epithelial cells in vivo. To assess the role of LMP1 in tumorigenic progression, transgenic mice were treated topically with chemical carcinogens. PyLMP1 mice were highly sensitive to chemical carcinogens, developing significantly more small papillomas at a faster rate than controls. Furthermore, LMP1 could substitute for 12-O-tetradecanoylphorbol-13-acetate treatment in tumor promotion. However, LMP1 inhibited expansion of the benign lesions and did not enhance progression of the lesions to carcinomas or the progression of these to the more malignant spindle cell carcinomas. These data demonstrate that, early in the carcinogenic process, LMP1 acts as a tumor promoter after chemical initiation; but, paradoxically, it may also introduce a hurdle against expansion or progression of a lesion.
9,10-Dimethyl-1,2-benzanthracene↗
Decreased sensitivity of tristetraprolin-deficient cells to p38 inhibitors suggests the involvement of tristetraprolin in the p38 signaling pathway.
Treatment of macrophages with pyridinyl imidazole inhibitors of p38 protein kinases can inhibit lipopolysaccharide-stimulated tumor necrosis factor alpha secretion. However, bone marrow-derived macrophages from tristetraprolin (TTP)-deficient mice were less sensitive than normal macrophages to this effect of p38 inhibitors, despite evidence for normal p38 activation in response to lipopolysaccharide. TTP is known to cause decreased stability of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor mRNAs after binding to an AU-rich element in their 3'-untranslated regions. A recombinant TTP fusion protein could be phosphorylated by a recombinant p38 kinase in cell-free assays and was phosphorylated to the same extent by immunoprecipitated p38 derived from normal and TTP-deficient cells stimulated with lipopolysaccharide; in both cases, the enzyme activity was inhibited by the p38 inhibitors. TTP phosphorylation also was increased in intact macrophages after lipopolysaccharide stimulation, an effect that was blocked by the p38 inhibitors. Finally, TTP in mammalian cell extracts bound less well to an AU-rich element RNA probe than did the same amount of TTP following dephosphorylation. These results suggest that TTP may be a component of the signaling cascade, initiated by inflammatory stimuli and mediated in part by activation of p38, that ultimately leads to enhanced secretion of tumor necrosis factor alpha.
3' Untranslated Regions↗
Medicines. Peace in a POD (patients' own drug).
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Humans↗
Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial.
BACKGROUND: Controlled trials suggest that leukotriene receptor antagonists can improve lung function and reduce requirement for oral or inhaled corticosteroids in patients with asthma. We aimed to assess whether montelukast, a leukotriene receptor antagonist, can improve symptoms or lung function in patients with chronic asthma with symptoms already taking corticosteroids. METHODS: We did a double-blind, placebo-controlled, crossover, randomised add-on study in which 100 patients with asthma and symptoms despite treatment with inhaled corticosteroids and additional therapy were given 10 mg montelukast sodium for 14 days in an outpatient clinic setting. Outcome measures were symptoms and peak flow diaries. FINDINGS: 72 patients had diary data for analysis. Compared with placebo, addition of montelukast did not result in any significant change in symptom scores (mean difference between the last 7 days of each treatment period 0.05; 95% CI --0.86 to 1.14), rescue inhaled beta(2) agonist use (mean difference in puffs per day 0.41; -0.29 to 0.57), or twice daily peak expiratory flow (PEF) measurements (mean difference in morning PEF 1.18 L/min; -14.29 to 17.14), and mean difference in evening peak flow (-0.50; -17.42 to 12.86). When treatment response was defined as a 15% or greater increase in mean peak flow readings, there were four responders to montelukast and seven responders to placebo. INTERPRETATION: Based on PEF data from our previous studies of a similar patient group we would have expected to detect changes of more than 5%. Used as additional therapy in a hospital outpatient clinic setting, montelukast did not provide such additional benefit in patients with moderate or severe asthma.
Acetates↗
Regulation of chicken gizzard ecto-ATPase activity by modulators that affect its oligomerization status.
The major ectonucleoside triphosphate phosphohydrolase in the chicken gizzard smooth muscle membranes is an ecto-ATPase, an integral membrane glycoprotein belonging to the E-ATPase (or E-NTPDase) family. The gizzard ecto-ATPase is distinguished by its unusual kinetic properties, temperature dependence, and response to a variety of modulators. Compounds that promote oligomerization of the enzyme protein, i.e., concanavalin A, chemical cross-linking agent, and eosin iodoacetamide, increase its activity. Compounds that inhibit some ion-motive ATPases, e.g., sulfhydryl reagents, xanthene derivatives, NBD-halides, and suramin, also inhibit the gizzard ecto-ATPase, but not another E-ATPase, the chicken liver ecto-ATP-diphosphohydrolase, which contains the same conserved regions as the ecto-ATPase. Furthermore, inhibition of the gizzard ecto-ATPase by these compounds as well as detergents is not prevented by preincubation of the membranes with the substrate, ATP, indicating that their interaction with the enzyme occurs at a locus other than the catalytic site. On the other hand, the inhibitory effect of these compounds, except suramin, is abolished or reduced if the membranes are preincubated with concanavalin A. It is concluded that these structurally unrelated modulators exert their effect by interfering with the oligomerization of the ecto-ATPase protein. Our findings suggest that, under physiological conditions, the gizzard smooth muscle ecto-ATPase may exhibit a range of activities determined by membrane events that affect the status of oligomerization of the enzyme.
4-Chloro-7-nitrobenzofurazan↗
Elevated motor threshold in drug-free, cocaine-dependent patients assessed with transcranial magnetic stimulation.
BACKGROUND: Transcranial magnetic stimulation (TMS) provides a noninvasive method of examining cortical inhibitory and excitatory processes and cortical excitability in awake subjects. There is evidence from clinical and electroencephalographic (EEG) data that cortical excitability may be abnormal in some psychiatric populations. Chronic cocaine abuse influences a number of neurotransmitters that are involved in the excitatory/inhibitory balance of the cerebral cortex. This pilot study was conducted to ascertain the possible utility of TMS in examining cortical excitability in a population of chronic cocaine abusers. METHODS: The right and left motor thresholds of ten cocaine-dependent subjects, according to DSM-IV, and ten normal control subjects were examined using single pulse TMS. RESULTS: The resting motor thresholds resulting from stimulation of the right or the left motor cortical regions were significantly elevated in cocaine-dependent subjects compared with matched control subjects. CONCLUSIONS: These pilot data suggest that chronic cocaine use significantly alters cortical excitability in the direction of increased inhibition or decreased excitability. We hypothesize that this observation reflects adaptation to those effects of cocaine intoxication that promote cortical excitability and seizures.
Adult↗
Bi-directional activation between human airway smooth muscle cells and T lymphocytes: role in induction of altered airway responsiveness.
Because both T lymphocyte and airway smooth muscle (ASM) cell activation are events fundamentally implicated in the pathobiology of asthma, this study tested the hypothesis that cooperative intercellular signaling between activated T cells and ASM cells mediates proasthmatic changes in ASM responsiveness. Contrasting the lack of effect of resting human T cells, anti-CD3-activated T cells were found to adhere to the surface of naive human ASM cells, increase ASM CD25 cell surface expression, and induce increased constrictor responsiveness to acetylcholine and impaired relaxation responsiveness to isoproterenol in isolated rabbit ASM tissues. Comparably, exposure of resting T cells to ASM cells prestimulated with IgE immune complexes reciprocally elicited T cell adhesion to ASM cells and up-regulated T cell expression of CD25. Extended studies demonstrated that: 1) ASM cells express mRNAs and proteins for the cell adhesion molecules (CAMs)/costimulatory molecules, CD40, CD40L, CD80, CD86, ICAM-1 (CD54), and LFA-1 (CD11a/CD18); 2) apart from LFA-1, ASM cell surface expression of the latter molecules is up-regulated in the presence of activated T cells; and 3) pretreatment of ASM cells and tissues with mAbs directed either against CD11a or the combination of CD40 and CD86 completely abrogated both the activated T cell-induced changes in expression of the above CAMs/costimulatory molecules in ASM cells and altered ASM tissue responsiveness. Collectively, these observations identify the presence of bi-directional cross-talk between activated T cells and ASM cells that involves coligation of specific CAMs/costimulatory molecules, and this cooperative intercellular signaling mediates the induction of proasthmatic-like changes in ASM responsiveness.
Adolescent↗
Screening for lung cancer.
BACKGROUND: The effectiveness of screening for lung cancer with chest radiography, sputum cytology or spiral CT has not been established. OBJECTIVES: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality. SEARCH STRATEGY: Electronic databases, bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest. DATA COLLECTION AND ANALYSIS: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effect model, but for other outcomes the fixed effect model was used. MAIN RESULTS: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT. REVIEWER'S CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.
Adult↗
Decreased natural killer (NK) cell function in chronic NK cell lymphocytosis associated with decreased surface expression of CD11b.
Chronic natural killer cell lymphocytosis (CNKL) is characterized by greatly increased numbers of natural killer (NK) cells and patients with this disease may survive for long periods. This is in contrast to patients with leukemic proliferations of NK cells who can have a rapidly progressive clinical course. We identified a pediatric patient who was largely healthy who had CNKL and we sought to determine if the expanded CD16(+)CD3(-) population in this patient functions differently than classical NK cells. Cytotoxic activity against NK cell-sensitive K562 target cells was present, but lower than that in control donors when calculated as lytic units per CD16(+)CD3(-) cell. This cytolytic activity was inducible in patient samples by IL-2/IL-12 stimulation proportionately to that induced in samples from control donors. Intracellular perforin was also present and induced in patient CD16(+)CD3(-) cells similarly to controls. Other presumed NK cell activities, such as IL-2/IL-12 induced IFN-gamma expression and initiation of apoptosis evidenced by annexin V binding after CD16 crosslinking were present in patient samples. Patient CD16(+)CD3(-) cells, however, differed from classical NK cells, as the majority did not express CD56, CD57, CD8, or CD11b. Most convincingly, there was a 5 log decrease in CD11b expression in patient CD16(+)CD3(-) cells compared to control as determined by mean channel fluorescence. These observed differences may explain the relatively benign phenotype of this disorder.
Apoptosis↗
Identification, genomic organization, and mRNA expression of LACTB, encoding a serine beta-lactamase-like protein with an amino-terminal transmembrane domain.
Database searching with bacterial serine beta-lactamases identified mouse expressed sequence tags (ESTs) with significant similarity scores.The cloned mouse cDNA encodes a novel 551-amino-acid protein, LACTB, with a predicted amino-terminal transmembrane domain but no signal peptide. It contains an active site motif related to C-class beta-lactamases. Homologues were detected in sequence data from human, rat, cow, rabbit, pig, toad, zebrafish, and Caenorhabditis elegans, but not in Saccharomyces cerevisiae or Drosophila melanogaster. The genes were mapped to human chromosome 15q22.1 and mouse chromosome 9. Sequencing of a 14.7-kb fragment of mouse genomic DNA defined six exons. A virtual human cDNA and a 549-residue protein, predicted from unfinished genomic sequence, showed the same intron/exon structure. Northern blot analysis showed expression of the 2.3-kb mRNA predominantly in mouse liver and human skeletal muscle. This is the first reported vertebrate example of this microbial peptidase family.
Amino Acid Sequence↗
Dipstick urinalysis and the accuracy of the clinical diagnosis of urinary tract infection.
The aim of this study was to determine whether dipstick urinalysis (DU) augmented the accuracy of clinical assessment in the diagnosis of urinary tract infection (UTI). The study was performed in 627 consecutive patients attending an adult emergency department (ED) in whom the clinical diagnosis of UTI was considered. We excluded 227 patients. Treating clinicians gave the probability of a UTI on an ordinal and continuous scale, before and after DU. The assigned clinical probabilities were then compared to the results of formal urine culture. The areas under receiver-operating characteristic curves (AUC) were calculated. We found that clinical assessment alone was effective in detecting those patients with a UTI from those without (AUC 0.75; p < 0.0001). There was, however, a statistically significant difference in the accuracy of diagnosing UTI after DU (AUC 0.87; p < 0.0001). Proportionately more patients with a moderate pre-test probability of UTI were re-assigned to a different probability rating following DU, compared to the low or high pre-test probability groups (p < 0.001). We conclude that DU in combination with clinical assessment is a superior method for diagnosing UTI than clinical assessment alone.
Adult↗
Variation in fleece characteristics of Awassi sheep at different ages.
Fleece characteristics have economic significance in sheep. When assessing fiber characteristics, the importance of sex, age of sheep and the body location of the sample taken are important considerations. Triplicate fleece samples were obtained from the shoulder, right mid-side and hip of 12 male and 17 female lambs (6-10 months), 62 yearling ewes (14-20 months) and 235 mature ewes (28-84 months) by hand shearing. The greasy fleece weight, staple length, fiber length and fiber diameter measures were 2.1+/-0.03kg, 14+/-0.18cm, 24+/-0.26cm and 36+/-0.33&mgr;m, respectively. Correspondingly, the medullated fibers, inner coat, outer coat and kemp fibers were 11.6+/-0.33, 59.7+/-0.29, 34.0+/-0.23 and 6.3+/-0.16%, respectively. Age had a significant influence on body weight and greasy fleece weight, but male and females were similar. Body location of the sample had a significant effect on the fiber diameter, and percentages of medullated fibers, kemp fibers, and inner coat fibers. The finest fibers and a lower percentage of medullated fibers were found on the shoulder and mid-side, whereas, the percentage of inner coat fibers was highest on the hip. Although there was no significant interaction between body location and age-sex groups for fiber characteristics, it was important for staple and fiber length (P<0.05). The wide variation in fiber diameter and percentage of medullated fibers suggest potential for improvement of economical traits.
Journal Article↗
Hepatitis B immunization of healthy elderly adults: relationship between naïve CD4+ T cells and primary immune response and evaluation of GM-CSF as an adjuvant.
The efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance the primary immune response to hepatitis B vaccine was studied in healthy elderly with young volunteers included as controls in this double-blind, placebo-controlled trial of GM-CSF as an immune adjuvant. Naïve T-helper cells (CD4+CD45RA+) were determined at baseline. Forty-five healthy elderly (average age, 74 years) and 37 healthy young controls (average age, 28 years) were randomized. Hepatitis B vaccine was administered at 0, 1, and 6 months. GM-CSF as a single injection of either 80 microg or 250 microg with the first and second doses of hepatitis B vaccine. In this trial GM-CSF did not enhance antibody responses. However, the antibody responses were dramatically different between these two groups: 35/35 young developed a protective titer versus 19/45 elderly (P < 0.0001). In addition, the mean logarithm of anti-hepatitis B antibody level in the 35 young who completed the study was 3.17 (log mIU/ml) but only 2.21 in the 19 elderly responders (P < 0.0001). Naïve T-helper cells differed significantly between the two groups: the mean percentage of CD4+CD45RA+ T cells was 47.9% versus 35.0% (P < 0.0001) in the young and elderly volunteers respectively. Naïve T cells also differed significantly between elderly who did or did not respond to HBV (39.9% vs. 31.7%, P = 0.039). Using linear regression, age, and percent naive, CD4 T cells were determined to significantly influence the anti-hepatitis B antibody response, but sex and dose of GM-CSF did not. For a two-parameter model: logarithm of antibody titer = (-0.038 x age in years) + (0.031 x % naïve CD4T cells) + 2.68; adjusted r2 = 0.605 and P < 0.0001. However, age had a larger effect than naive CD4 T cells, i.e., in comparing young and elderly groups the log antibody titer decreased by 1.73 due to the increase in age but only 0.40 due to the decrease in naive CD4 T cells. Thus, there was a large effect of age that could not be explained by the quantitative change in the naïve T-helper cells.
Adjuvants, Immunologic↗
Combining the analyses of introgressive hybridisation and linkage mapping to investigate the genetic architecture of population divergence in the lake whitefish (Coregonus clupeaformis, Mitchill).
Adaptation and reproductive isolation, the engines of biological diversity, are still elusive when discussing the genetic bases of speciation. Namely, the number of genes and magnitude of selection acting positively or negatively on genomic traits implicated in speciation is contentious. Here, we describe the first steps of an ongoing research program aimed at understanding the genetic bases of population divergence and reproductive isolation in the lake whitefish (Coregonus clupeaformis). A preliminary linkage map originating from a hybrid cross between dwarf and normal ecotypes is presented, whereby some of the segregating AFLP markers were found to be conserved among natural populations. Maximum-likelihood was used to estimate hybrid indices from non-diagnostic markers at 998 AFLP loci. This allowed identification of the most likely candidate loci that have been under the influence of selection during the natural hybridisation of whitefish originating from different glacial races. As some of these loci could be identified on the linkage map, the possibility that selection of traits in natural populations may eventually be correlated to specific chromosomal regions was demonstrated. The future prospects and potential of these approaches to elucidate the genetic bases of adaptation and reproductive isolation among sympatric ecotypes of lake whitefish is discussed.
Animals↗